{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:19Z","timestamp":1792790359201,"version":"4.5.0"},"posted":{"date-parts":[[2026,10,1]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stanford University Medical Scientist Training Program","award":["T32-GM007365"],"award-info":[{"award-number":["T32-GM007365"]}],"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Post-treatment Lyme disease syndrome (PTLDS) is characterized by persistent symptoms after antibiotic therapy for\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  infection. The mechanisms underlying these symptoms remain incompletely understood and have been attributed to ongoing low-level infection, autoimmunity, or immune dysregulation driven by residual bacterial antigens. We investigated whether\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  protein antigen persists in long-lived monocyte subsets in PTLDS patients and is associated with broader immune dysregulation. CD14\n                  <jats:sup>\u207a<\/jats:sup>\n                  CD16\n                  <jats:sup>\u207a<\/jats:sup>\n                  monocytes from 10 patients with PTLDS were analyzed by mass spectrometry; plasma from all 10 was profiled on a 14-plex cytokine panel against 50 healthy donors; PBMCs from 6 patients (3 antigen-positive and 3 antigen-negative) underwent RT-qPCR and bulk RNA-seq with immune-compartment profiling. FlaB and OspC were detected in CD14\n                  <jats:sup>\u207a<\/jats:sup>\n                  CD16\n                  <jats:sup>\u207a<\/jats:sup>\n                  monocytes months to years after treatment, whereas\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  transcript was not detected. Plasma IFN-\u03b3 exceeded the healthy donor median in all 10 participants. Antigen-positive samples showed an antigen-associated inflammatory transcriptional profile, including increased TNFSF14\/LIGHT, GSDMD, GBP5, and KCNJ2 expression, together with a compartment-level pattern of monocyte-skewed myeloid reconfiguration, higher neutrophil-related features, and selective T-cell-state changes. These findings link residual\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  protein in CD14\n                  <jats:sup>\u207a<\/jats:sup>\n                  CD16\n                  <jats:sup>\u207a<\/jats:sup>\n                  monocytes to monocyte-skewed immune remodeling in PTLDS, paralleling observations in long COVID and supporting a model in which post-infectious syndromes are sustained by antigen-fueled immune remodeling rather than ongoing infection.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>\n                    Many people treated for Lyme disease go on to experience fatigue, pain, and difficulty thinking for months or years, and the reason is unknown. Persistent infection has been a leading explanation, yet longer courses of antibiotics do not help. We found proteins from\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    , the bacterium that causes Lyme disease, inside long-lived blood monocytes of patients with lasting symptoms, years after treatment and with no sign that the bacterium was still active. Patients carrying these proteins showed a distinct inflammatory immune profile. These findings point to leftover bacterial material, rather than ongoing infection, as a possible driver of persistent symptoms, echo observations in long COVID, and argue that treatments directed at the immune response deserve study.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.24.26363601","type":"posted-content","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:55:12Z","timestamp":1790884512000},"source":"Crossref","is-referenced-by-count":0,"title":["Persistent\n                  <i>Borrelia burgdorferi<\/i>\n                  protein antigen in CD16\n                  <sup>+<\/sup>\n                  monocytes is associated with monocyte-skewed immune dysregulation in post-treatment Lyme disease syndrome (PTLDS)"],"prefix":"10.64898","author":[{"given":"Bruce K.","family":"Patterson","sequence":"first","affiliation":[{"name":"HealthBio Inc., Traverse City, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar B.","family":"Francisco","sequence":"additional","affiliation":[{"name":"HealthBio Inc., Traverse City, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Caucell Inc., Driggs, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwat","family":"Medetgul-Ernar","sequence":"additional","affiliation":[{"name":"Caucell Inc., Driggs, ID, USA"},{"name":"Biophysics Program, Stanford University, Stanford, CA, USA"},{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Beaty","sequence":"additional","affiliation":[{"name":"HealthBio Inc., Traverse City, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaeden","family":"Beaty","sequence":"additional","affiliation":[{"name":"HealthBio Inc., Traverse City, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Felder","sequence":"additional","affiliation":[{"name":"HealthBio Inc., Traverse City, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Yogendra","sequence":"additional","affiliation":[{"name":"HealthBio Inc., Traverse City, MI, USA"},{"name":"Lawrence General Hospital, Lawrence, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100519250536000_2026.09.24.26363601v1.1","unstructured":"CDC. Lyme Disease Surveillance and Data [Internet]. Lyme Dis. 2025. https:\/\/www.cdc.gov\/lyme\/data-research\/facts-stats\/index.html. Accessed March 3, 2026."},{"issue":"1","key":"2026100519250536000_2026.09.24.26363601v1.2","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1038\/nrdp.2016.90","article-title":"Lyme borreliosis","volume":"2","year":"2016","journal-title":"Nat Rev Dis Primer"},{"key":"2026100519250536000_2026.09.24.26363601v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.200221797"},{"key":"2026100519250536000_2026.09.24.26363601v1.4","unstructured":"UpToDate [Internet]. https:\/\/www.uptodate.com\/contents\/clinical-manifestations-of-lyme-disease-in-adults. 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